Abstract
Activity in numerous brain regions drives heroin seeking, but no circuits that limit heroin seeking have been identified. Furthermore, the neural circuits controlling opioid choice are unknown. In this study, we examined the role of the infralimbic cortex (IL) to nucleus accumbens shell (NAshell) pathway during heroin choice and relapse. This model yielded subpopulations of heroin versus food preferring rats during choice, and choice was unrelated to subsequent relapse rates to heroin versus food cues, suggesting that choice and relapse are distinct behavioral constructs. Supporting this, inactivation of the IL with muscimol produced differential effects on opioid choice versus relapse. A pathway-specific chemogenetic approach revealed, however, that the IL-NAshell pathway acts as a common limiter of opioid choice and relapse. Furthermore, dendritic spines in IL-NAshell neurons encode distinct aspects of heroin versus food reinforcement. Thus, opioid choice and relapse share a common addiction-limiting circuit in the IL-NAshell pathway.
Highlights
Activity in numerous brain regions drives heroin seeking, but no circuits that limit heroin seeking have been identified
These results indicate that rats have a higher motivation for heroin and that heroin is considered more essential at higher price points than food reward in this model
No differences were observed in the cumulative frequency distribution of spine head diameter between heroin versus food prefers (Fig. 6i), and no other significant correlations were observed besides those reported above. These results identify the first neural circuit that acts as an endogenous limiter of heroin seeking, namely the infralimbic cortex (IL)→nucleus accumbens shell (NAshell) pathway
Summary
Activity in numerous brain regions drives heroin seeking, but no circuits that limit heroin seeking have been identified. Some components of the opioid relapse circuitry have been established, including projections from the prefrontal cortex to the nucleus accumbens, a proposed final common pathway to relapse This projection is functionally segregated into a dorsal and a ventral circuit[2,3]. While pharmacological manipulations of the IL and the NAshell suggest a driver function for these individual brain regions in heroin relapse[5,6,7], a pathwayspecific approach for this circuit has not been explicitly utilized in animal models of opioid seeking Such an approach has revealed a limiter function for the IL→NAshell pathway for both cocaine and alcohol seeking[8,9,10,11,12]. The data support a common limiter function for the IL→NAshell pathway in heroin seeking under both choice and relapse conditions
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